Spider silk erectile nerve reconstruction in robot-assisted radical prostatectomy: a first-in-men feasibility analysis.

PURPOSE: To investigate the safety and feasibility of spider silk interposition for erectile nerve reconstruction in patients undergoing robotic radical prostatectomy (RARP). METHODS: The major-ampullate-dragline from Nephila edulis was used for spider silk nerve reconstruction (SSNR). After removal of the prostate with either uni- or bilateral nerve-sparing, the spider silk was laid out on the site of the neurovascular bundles. Data analysis included inflammatory markers and patient reported outcomes. RESULTS: Six patients underwent RARP with SSNR. In 50% of the cases, only a unilateral nerve-sparing was performed, bilateral nerve-sparing could be performed in three patients. Placement of the spider silk conduit was uneventful, contact of the spider silk with the surrounding tissue was mostly sufficient for a stable connection with the proximal and distal ends of the dissected bundles. Inflammatory markers peaked until postoperative day 1 but stabilized until discharge without any need for antibiotic treatment throughout the hospital stay. One patient was readmitted due to a urinary tract infection. Three patients reported about erections sufficient for penetration after three months with a continuous improvement of erectile function both after bi- and unilateral nerve-sparing with SSNR up to the last follow-up after 18 months. CONCLUSION: In this analysis of the first RARP with SSNR, a simple intraoperative handling without major complications was demonstrated. While the series provides evidence that SSNR is safe and feasible, a prospective randomized trial with long-term follow-up is needed to identify further improvement in postoperative erectile function due to the spider silk-directed nerve regeneration.

Identification of a Novel Renal Metastasis Associated CpG-Based DNA Methylation Signature (RMAMS).

Approximately 21% of patients with renal cell cancer (RCC) present with synchronous metastatic disease at the time of diagnosis, and metachronous metastatic disease occurs in 20-50% of cases within 5 years. Recent advances in adjuvant treatment of aggressive RCC following surgery suggest that biomarker-based prediction of risk for distant metastasis could improve patient selection. Biometrical analysis of TCGA-KIRC data identified candidate loci in the NK6 homeobox 2 gene (NKX6-2) that are hypermethylated in primary metastatic RCC. Analyses of NKX6-2 DNA methylation in three gene regions including a total of 16 CpG sites in 154 tumor-adjacent normal tissue, 189 RCC, and 194 metastatic tissue samples from 95 metastasized RCC patients revealed highly significant tumor-specific, primary metastatic-specific, and metastatic tissue-specific hypermethylation of NKX6-2. Combined CpG site methylation data for NKX6-2 and metastasis-associated genes (INA, NHLH2, and THBS4) demonstrated similarity between metastatic tissues and metastatic primary RCC tissues. The random forest method and evaluation of an unknown test cohort of tissues using receiver operator characteristic curve analysis revealed that metastatic tissues can be differentiated by a median area under the curve of 0.86 (p = 1.7 × 10-8-7.5 × 10-3) in 1000 random runs. Analysis of variable importance demonstrated an above median contribution for decision-making of at least one CpG site in each of the genes, suggesting superior informativity for sites annotated to NHLH2 and NKX6-2. Thus, DNA methylation of NKX6-2 is associated with the metastatic state of RCC tissues and contributes to a four-gene-based statistical predictor of tumoral and metastatic renal tissues.

DNA methylation of tumor associated calcium signal transducer 2 (TACSTD2) loci shows association with clinically aggressive renal cell cancers.

BACKGROUND: DNA methylation is frequently observed in the development and progression of many human tumors as well as renal cell cancer (RCC). Tumor Associated Calcium Signal Transducer 2 (TACSTD2) participates in cell cycle progression through MAPK signalling pathway activation. Moreover, tumor-specific hypermethylation and association with aggressive cancer characteristics has been found for lung adenocarcinoma, hepatocellular carcinoma and cholangiocarcinoma. Whether TACSTD2 is tumor specifically hypermethylated in RCC or shows association of methylation with adverse clinicopathological parameters and survival of patients has not been investigated at yet. METHODS: Quantitative methylation-specific PCR (qMSP) analysis of a locus in the intron 1 region of TACSTD2 gene was carried out in a cross-sectional study of 127 paired RCC and normal samples. In silico analysis of TACSTD2 methylation in the TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset of 280 patients served as validation cohort. Statistical analyses were carried out using the two-sided paired t-test for matched tumor and normal sample comparisons, logistic regression for subgroup comparisons, Cox regression for analysis of recurrence free survival (RFS) and Pearson correlation analysis for correlation of TACSTD2 methylation and TACSTD2 mRNA in KIRC data. RESULTS: Higher methylation levels in RCC were significantly associated with advanced disease (p < 0.001), high tumor stage (p = 0.003), tumor differentiation (p = 0.033) and presence of lymph node (p = 0.021) or distant metastases (p = 0.008). TACSTD2 hypermethylation was associated with a shorter RFS of patients and demonstrate statistical independency from clinical parameters as state of metastasis, tumor stage, grade and state of advanced disease. In silico validation using TCGA KIRC data also demonstrated association of TACSTD2 loci with adverse clinicopathology and shortened RFS of patients. In addition, in silico analyses of TCGA KIRC data showed an inverse correlation between DNA methylation levels of TACSTD2 and mRNA expression. CONCLUSIONS: Our results suggest an association between TACSTD2 methylation and disease progression and clinical course of RCC.

An advanced method for the immunohistochemical detection of nitric oxide synthase (NOS) in the female genital tract.

The expression of nitric oxide synthase (NOS) in male and female urogenital tissues has been investigated by using conventional light microscopical immunoperoxidase staining. We present an improved immunohistochemical method for the specific and simultaneous detection of endothelial and neuronal NOS (eNOS/nNOS) in vaginal tissue. Specific antibodies have been used in combination with the tyramide signal amplification method. We found a subepithelial meshwork of varicose nerve fibers. A subpopulation of fibers presented immunoreactivity specific for nNOS. Epithelial cells also showed cytoplasmatic labeling for nNOS. Arteries presenting signals for eNOS in their endothelial layer were found in close proximity to nNOS-positive nerve fibers.

Efficacy of repeated PSMA PET-directed radiotherapy for oligorecurrent prostate cancer after initial curative therapy.

PURPOSE: To assess the outcome of prostate cancer (PCa) patients diagnosed with oligorecurrent disease and treated with a first and a second PSMA (prostate-specific membrane antigen ligand) PET(positron-emission tomography)-directed radiotherapy (RT). PATIENTS AND METHODS: Thirty-two patients with oligorecurrent relapse after curative therapy received a first PSMA PET-directed RT of all metastases. After biochemical progression, all patients received a second PSMA PET-directed RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS) and androgen deprivation therapy-free survival (ADT-FS). The intervals of BPFS were analyzed separately as follows: the interval from the last day of PSMA PET-directed RT to the first biochemical progression was defined as bPFS_1 and the interval from second PSMA PET-directed RT to further biochemical progression was defined as bPFS_2. RESULTS: The median follow-up duration was 39.5 months (18-60). One out of 32 (3.1%) patients died after 47 months of progressive metastatic prostate cancer (mPCa). All patients showed biochemical responses after the first PSMA PET-directed RT and the median prostate-specific antigen (PSA) level before RT was 1.70 ng/mL (0.2-3.8), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range <0.07-3.8; p = 0.004). The median PSA level at biochemical progression after the first PSMA PET-directed RT was 2.9 ng/mL (range 0.12-12.80; p = 0.24). Furthermore, the PSA level after the second PSMA PET-directed RT at the last follow-up (0.52 ng/mL, range <0.07-154.0) was not significantly different (p = 0.36) from the median PSA level (1.70 ng/mL, range 0.2-3.8) before the first PSMA PET-directed RT. The median bPFS_1 was 16.0 months after the first PSMA PET-directed RT (95% CI 11.9-19.2) and the median bPFS_2 was significantly shorter at 8.0 months (95% CI 6.3-17.7) after the second PSMA PET-directed RT (p = 0.03; 95% CI 1.9-8.3). Multivariate analysis revealed no significant parameter for bPFS_1, whereas extrapelvic disease was the only significant parameter (p = 0.02, OR 2.3; 95% CI 0.81-4.19) in multivariate analysis for bPFS_2. The median ADT-FS was 31.0 months (95% CI 20.1-41.8) and multivariate analysis showed that patients with bone metastases, compared to patients with only lymph node metastases at first PSMA PET-directed RT, had a significantly higher chance (p = 0.007, OR 4.51; 95% CI 1.8-13.47) of needing ADT at the last follow-up visit. CONCLUSION: If patients are followed up closely, including PSMA PET scans, a second PSMA PET-directed RT represents a viable treatment option for well-informed and well-selected patients.

Impact of double J stenting or nephrostomy placement during transurethral resection of bladder tumour on the incidence of metachronous upper urinary tract urothelial cancer.

BACKGROUND: Whether or not double J (DJ) stenting during transurethral resection of a bladder tumour (TURBT) harms patients with regard to possible metachronous upper urinary tract urothelial cancer (UUTUC) development remains controversial. This study evaluated the impact of DJ compared to nephrostomy placement during TURBT for bladder cancer (BCa) on the incidence of metachronous UUTUCs. METHODS: We retrospectively analysed 637 patients who underwent TURBT in our department between 2008 and 2016. BCa, UUTUC and urinary drainage data (retrograde/anterograde DJ and percutaneous nephrostomy) were assessed, along with the prevalence of hydronephrosis, and mortality. Chi-square and Fisher's exact test was performed for univariate analyses. Survival analysis was performed by the Kaplan-Meier method and log-rank tests. RESULTS: UUTUC was noted in 28 out of 637 patients (4.4%), whereas only eight (1.3%) developed it metachronously to BCa. Out of these, four patients received DJ stents, while four patients received no urinary drainage of the upper urinary tract. Placement of urinary drainage significantly correlated with UUTUC (50.0% vs. 17.9%; p = 0.041). DJ stenting significantly correlated with UUTUC (50.0% vs. 11%; p <  0.01), while no patient with a nephrostomy tube developed UUTUC. UUTUC-free survival rates were significantly lower for patients with DJ stents than for all other patients (p = 0.001). Patients with or without DJ stents had similar overall survival (OS) rates (p = 0.73), whereas patients with nephrostomy tubes had significantly lower OS rates than all other patients (p <  0.001). CONCLUSIONS: Patients with DJ stenting during TURBT for BCa might have an increased risk of developing metachronous UUTUC. This study indicated advantages in placing nephrostomy tubes rather than DJ stents; however, confirmation requires investigation of a larger cohort. Even so, the increased mortality rate in the nephrostomy group reflected hydronephrosis as an unfavourable prognostic factor.

Emerging drugs to target lower urinary tract symptomatology (LUTS)/benign prostatic hyperplasia (BPH): focus on the prostate.

OBJECTIVES: The benign prostatic syndrome, comprising lower urinary tract symptomatology secondary to benign prostatic hyperplasia/enlargement, represents a major health care issue in westernized countries. The pharmacological management involves alpha-adrenoceptor antagonists, intervention into the hormonal control of prostate growth using inhibitors of the enzyme 5-alpha-reductase, and stimulation of the nitric oxide/cyclic GMP pathway by tadalafil, an inhibitor of the phosphodiesterase type 5. METHODS: This review summarizes the achievements which have been made in the development of drug candidates assumed to offer opportunities as beneficial treatment options in the management of the benign prostatic syndrome. RESULTS: A review of the literature has revealed that the line of development is focusing on drugs interfering with peripheral neuromuscular/neuronal mechanisms (nitric oxide donor drugs, agonists/antagonists of endogenous peptides, botulinum toxin, NX-1207), the steroidal axis (cetrorelix) or the metabolic turn-over (lonidamine), as well as the combination of drugs already established in the treatment of lower urinary tract symptomatology/benign prostatic hyperplasia (phosphodiesterase 5 inhibitor plus alpha-adrenoceptor antagonist). CONCLUSION: Many research efforts have provided the basis for the development of new therapeutic modalities for the management of lower urinary tract dysfunctions, some of which might be offered to the patients in the near future.

Comparison of 68 Ga-PSMA ligand PET/CT versus conventional cross-sectional imaging for target volume delineation for metastasis-directed radiotherapy for metachronous lymph node metastases from prostate cancer.

PURPOSE: To assess the differences in the target volume (TV) delineation of metachronous lymph node metastases between 68 Ga-PSMA ligand PET/CT and conventional imaging in a comparative retrospective contouring study. PATIENTS AND METHODS: Twenty-five patients with biochemical prostate cancer recurrence after primary prostatectomy underwent 68 Ga-PSMA ligand PET/CT in addition to conventional imaging techniques such as CT and/or MR imaging for restaging. All patients were diagnosed with at least one lymph node metastasis. TVs were manually delineated in two different ways: (a) based on conventional imaging (CT/MRI) and (b) based on conventional imaging (CT/MRI) plus 68 Ga-PSMA ligand PET/CT. The size of TVs, overlap rates, and subjective assessment of the difficulty of TV delineation reported by the radiation oncologist (easy/moderate/difficult) were compared. RESULTS: With the additional information from PSMA ligand PET, 47 lymph node metastases were identified and included in the gross tumor volume (GTV). The median clinical target volume (CTV) of non-PET-based TV delineation was statistically larger than the CTV based on PET imaging (134.8 ml [range 6.9-565.2] versus 44.9 ml [range 4.9-481.3; p = 0.001]). The CTV based on CT/MRI enclosed only 81.3% (39/48) of PET-positive lymph nodes. The CT/MRI-based CTV did not enclose all PET-positive lymph nodes in 24% (6/25) of patients. In 12% (3/25) of patients, all PET-positive lymph nodes were outside of the CT/MRI-based CTV. The median overlap rates (TVPET/TVCT/MRIâ€¯× 100) were 45.7% (range 0-96.9) for the GTV and 71.7% (range 9.8-98.2) for the CTV. The assessment of difficulty of contouring revealed that contouring with the additional imaging information of the PET was categorized as easy/moderate in 92% (23/25) and as difficult in 8% (2/25) of the cases, whereas contouring based on CT/MRI without PET was categorized as difficult in 56% (14/25) and as easy/moderate in 44% of the cases (11/25; p = 0.003). CONCLUSION: 68 Ga-PSMA ligand PET/CT is superior to conventional cross-sectional imaging for the delineation of lymph node metastases from prostate cancer. PET-based TV delineation allows for smaller target volumes and should be considered the standard for irradiation of metachronous lymph node metastases in recurrent prostate cancer. Conventional imaging is not sufficiently sensitive for radio-oncological treatment concepts in oligometastatic prostate cancer.

Course of transforming growth factor ß1 in the systemic and cavernous blood of healthy males through different penile conditions.

Studies on erectile dysfunction (ED) have revealed a relationship between smooth muscle atrophy and the accumulation of collagen in the corpus cavernosum (CC). Transforming growth factor ß1 (TGF ß1) is a cytokine which has been proposed to be involved in the fibrotic process in the CC. We aimed to evaluate the course of TGF ß1 in the systemic and cavernous blood of 17 healthy males through different phases of the sexual arousal response (exemplified by the penile conditions flaccidity, tumescence, rigidity and detumescence). An enzyme-linked immunoassay was used to measure the concentration of TGF ß1 (ng/ml) in both the systemic and cavernous blood at the stages of flaccidity, tumescence and detumescence. TGF levels were significantly higher in the cavernous compartment than in the systemic blood. A linear decrease was evident in the cavernous blood when the flaccid penis became tumescent (24.3 ± 14.5 to 13.9 ± 6.5) and rigid (to 8.7 ± 3.1). At detumescence, TGF increased to 18.3 ± 10.4. In contrast, the levels in the systemic circulation remained unchanged. The results are in support of the hypothesis that the concentration of TGF ß1 in the CC is regulated by adequate blood flow and oxygenation.

Arginase enzymes in the human prostate: A molecular biological and immunohistochemical approach.

The nitric oxide (NO) pathway plays a role in maintaining the function of the prostate. An impairment in the activity of the NO system may have an impact in the manifestation of lower urinary tract symptomatology and benign prostatic hyperplasia. Arginase enzymes (Arg) counteract the generation of NO by depleting the intracellular pool of L-arginine, known to be the substrate of the NO synthases. This study investigated the expression of arginase type I and II in the human prostate. Nondiseased prostate tissue was obtained during pelvic surgeries (prostatectomy, cystoprostatectomy). Tissue sections were exposed to antibodies directed against Arg I and II, cGMP, the phosphodiesterase 5 and nNOS. The expression of mRNA transcripts encoding for Arg I and Arg II was investigated using molecular biology. Reverse transcriptase polymerase chain reaction (RT-PCR) revealed the presence of mRNA encoding for Arg I and II, immunofluorescence specific for Arg I was seen in the stromal smooth musculature, and labelling for PDE5 and cyclic GMP was also observed. Nerve fibres containing nNOS were identified running across the smooth musculature. Immunostainings for Arg II did not yield signals. These findings are in support of the notion that, in the prostate, Arg is involved in the modulation of the activity of the NO system.

Patterns of relapse as determined by 68Ga-PSMA ligand PET/CT after radical prostatectomy : Importance for tailoring and individualizing treatment.

PURPOSE: To evaluate the patterns of relapse and impact on the intended treatment when using 68Ga-prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) imaging for restaging of disease in patients with biochemical relapse after radical prostatectomy (RP) before salvage radiotherapy (sRT). METHODS: In all, 39 patients with biochemical recurrence after RP who had no primary indication for adjuvant RT due to the absence of biologically unfavorable disease (e.g., extracapsular extension, seminal vesicle invasion, positive margins, or lymph node involvement) underwent a 68Ga-PSMA ligand PET/CT for planning of sRT. RESULTS: PET/CT was positive in 84.6% (33/39) of patients. A total of 61 lesions were observed in these patients (on average 1.8 lesions per patient); 30.3% (10/33) of patients had locally recurrent disease in the prostatic bed. The clinical TNM stage (TNM: tumour-lymph nodes-metastasis-classification) was altered in 69.7% (23/33) of patients following PET, resulting in individualized treatment concepts. A prostate-specific antigen (PSA) >1.0 ng/mL was significantly associated with an increased risk of extrapelvic metastatic disease (p = 0.048). The PSA level at the time of PSMA ligand PET/CT correlated with the peak standardized uptake value (SUVpeak; p = 0.002). According to current clinical guidelines, the remaining 15.4% (6/39) of patients without evidence of disease on PET received sRT with a dose of 66.0 Gy. CONCLUSION: Our results suggest that in patients with biochemical recurrence who did not receive early sRT, a 68Ga-PSMA ligand PET/CT for restaging of disease allows for tailoring and individualizing treatment. Particularly in patients with PSA levels above 1.0 ng/mL, a 68Ga-PSMA ligand PET/CT should be performed for therapy planning, since patients often have metastases not confined to the pelvis.

Is ß-endorphin significant in the control of the male sexual response?

It has been assumed that ß-endorphin, belonging to the family of opiodergic neuropeptides, might facilitate the inhibition of the male sexual response; however, its role in the control of the penile erectile tissue remains to be elucidated. This study aimed to evaluate in healthy men the course of ß-endorphin in the systemic and cavernous blood through different stages of sexual arousal. Thirty-four (34) men were exposed to erotic stimuli to induce penile tumescence and rigidity. Blood was aspirated from the corpus cavernosum and a cubital vein during the penile conditions flaccidity, tumescence, rigidity and detumescence. Plasma levels of ß-endorphin were determined by means of radioimmunometric methods. The effects of ß-endorphin on isolated human penile erectile tissue were investigated in vitro. ß-endorphin did not induce a contractile response of the cavernous tissue or reverse the contraction induced by noradrenaline. ß-endorphin decreased in the systemic blood when the penis became tumescent and rigid and increased during detumescence. In the cavernous blood, no alterations in ß-endorphin concentrations were observed. The drop in ß-endorphin observed during tumescence and rigidity seems likely to reflect the inhibition of the opioidergic input with the beginning of sexual arousal.

Deep Surgical Site Infections after Open Radical Cystectomy and Urinary Diversion Significantly Increase Hospitalisation Time and Total Treatment Costs.

INTRODUCTION: Deep surgical site infections (DSSI) usually require secondary treatments. The aim of this study was to compare the total length of hospitalisation (LOH), intensive care unit (ICU) duration, and total treatment costs in patients with DSSI versus without DSSI after open radical cystectomy (ORC) and urinary diversion. MATERIAL AND METHODS: Prospective case-control study in a tertiary care hospital in patients after ORC with urinary diversion during April 2008 to July 2012. DSSI was defined based on Centers for Disease Control and Prevention criteria. Matched-pair analysis for patients with versus without DSSI was done in 1:2 ratios. Patients with superficial surgical site infections (SSI) were excluded from analysis. RESULTS: In total, 189 operations were performed. Thirty-eight patients (20.1%) developed SSI of which 28 patients (14.8%) had DSSI. Out of 28 patients, 27 (96.4%) were with DSSI and required surgical re-intervention. Due to insufficient matching criteria, 11 patients with DSSI were excluded from analyses. Consequently, 17 patients with DSSI were matched with 34 patients without DSSI. Significant differences were seen for median overall LOH (30 vs. 18 days, p < 0.001), median ICU duration (p = 0.024), and median overall treatment costs (€17,030 vs. €11,402, p = 0.011). CONCLUSIONS: DSSI significantly increases LOH (67%) and treatment costs (49%), adding up to a financial loss for the hospital of approximately €5,500 in patients with DSSI.

Laparoendoscopic partial nephrectomy in single-incision triangulated umbilical surgery (SITUS) technique: early experience.

BACKGROUND: Nephron sparing surgery for renal tumors has evolved as the standard of care for resectable renal tumors. Laparoscopic partial nephrectomy (PN) has gained recognition after technical refinements were able to match the well-established criteria for open partial nephrectomy. Laparoendoscopic surgery (LESS) is one of the approaches to further minimize invasiveness of laparoscopic surgery. OBJECTIVE: We report our initial experience with LESS partial nephrectomy in single-incision transumbilical surgery technique (SITUS) in daily clinical practice. DESIGN, SETTING, AND PARTICIPANTS: From 2010, patients undergoing SITUS-PN were prospectively evaluated. Patients with small, solitary or multiple, exophytic-enhancing renal masses were selected, whereas patients with solitary kidney, endophytic or hilar tumors were excluded. Important clinical data, PADUA and RENAL score, were assessed prospectively. MEASUREMENTS: Patients' characteristics, perioperative, hematologic and pathologic data as well as pain evaluation using the visual analogue pain scale (VAPS) were assessed. RESULTS AND LIMITATIONS: A total of 13 patients underwent LESS-PN/SITUS-PN (6 right and 7 left renal units). One patient was converted to conventional laparoscopy requiring two additional ports to treat bleeding from renal vessels. Pathology revealed renal cell carcinoma in nine patients, oncocytoma in one and benign cyst in three patients. No positive surgical margin was observed. The mean blood loss was 2.1 g/dl [range 0.5-4.5 g/dl] in hemoglobin. Minimal discomfort was noted at discharge (VAPS = 0.2 ± 0.6 [range 0-2]/10]. CONCLUSION: LESS partial nephrectomy in SITUS technique is feasible for selected exophytic tumors and has been integrated into our armamentarium for nephron sparing minimally invasive surgical treatment.

Long-term bowel disorders following radial cystectomy: an underestimated issue?

PURPOSE: Patients after radical cystectomy (RC) frequently complain about bowel disorders (BDs). Reports addressing related long-term complications are sparse. This cross-sectional study assessed changes in bowel habits (BH) after RC. METHODS: A total of 89 patients with a minimum follow-up ≥1 year after surgery were evaluated with a questionnaire. Patients with BD prior to surgery were excluded. Symptoms such as diarrhea, constipation, bloating/flatulence, incomplete defecation, uncontrolled stool loss, and impact on quality of life (QoL) were assessed. RESULTS: A total of 46.1 % of patients reported changes in BH; however, only 25.8 % reported experiencing related dissatisfaction. Primary causes of dissatisfaction were diarrhea and uncontrolled stool loss. The most common complaints were bloating/flatulence and the feeling of incomplete defecation, but these symptoms did not necessarily lead to dissatisfaction or impairment in quality of life. No difference was identified between an orthotopic neobladder and ileal conduit, and even patients without bowel surgery were affected. QoL, health status, and energy level were significantly decreased in unsatisfied patients. CONCLUSIONS: About 25 % of patients complain about BDs after RC. More prospective studies assessing symptoms, comorbidities, and dietary habits are necessary to address this issue and to identify strategies for follow-up recommendations.

Current evidence of transurethral Ho:YAG and Tm:YAG treatment of bladder cancer: update 2014.

INTRODUCTION: Bladder cancer (BC) represents a growing health care problem worldwide. In times of tight budgets and an aging society, new strategies for the transurethral treatment of BC are needed. Laser devices used for tumor vaporization and/or en bloc resection provide an alternative to parvenu strategies. MATERIALS AND METHODS: Medline/Cochrane search was performed using following terms: bladder cancer, urothelial carcinoma, laser, en bloc, vaporization, photoablation, holmium, thulium, Ho:YAG, Tm:YAG, HoLRBT and TmLRBT. Last date of search was February 12, 2014. RESULTS: Eighteen publications in English were identified including 800 patients (Ho:YAG = 652 patients and Tm:YAG = 148 patients). Data on en bloc resection techniques were presented in 10 publications, 7 publications provided data of tumor vaporization and one publication presented data on both. Level of evidence based on SIGN is mainly 3 (non-analytic studies); only three studies are level 2 (prospective case control studies). Tumor vaporization seems to be a promising alternative for the treatment of recurrent tumors in selected patients. It can be performed in an office-based approach without the need of general anesthesia. The use of photodynamic diagnostic might enhance surgical quality. The principle of en bloc resection should provide accurate staging in most cases; however, data on this important aspect are missing. Peri- and postoperative complications are scarce. Due to the nature of the energy source, bladder perforation caused by obturator nerve reflex is highly unlikely when using lasers. There is a trend toward decreased infield recurrence rates. CONCLUSIONS: Lasers are potentially useful alternatives to conventional TURBT, but systematical assessments using standardized classification systems and well-designed RCTs are needed to make results comparable.

Targeted MRI/TRUS fusion-guided biopsy in men with previous prostate biopsies using a novel registration software and multiparametric MRI PI-RADS scores: first results.

PURPOSE: To evaluate a novel system for MRI/TRUS fusion-guided biopsy for detection of prostate cancer (PCa) in patients with previous negative prostate biopsy and determine diagnostic accuracy when using the Prostate Imaging Reporting and Data System (PI-RADS) for multiparametric magnetic resonance imaging (mpMRI) as proposed by the European Society of Urogenital Radiology. METHODS: Thirty-nine men with clinical suspicion of PCa and history of previous prostate biopsy underwent mpMRI on a 3-T MRI. In total, 72 lesions were evaluated by the consensus of two radiologists. PI-RADS scores for each MRI sequence, the sum of the PI-RADS scores and the global PI-RADS were determined. MRI/TRUS fusion-guided targeted biopsy was performed using the BioJet™ software combined with a transrectal ultrasound system. Image fusion was based on rigid registration. PI-RADS scores of the dominant lesion were compared with histopathological results. Diagnostic accuracy was determined using receiver operating characteristic curve analysis. RESULTS: MRI/TRUS fusion-guided biopsy was reliable and successful for 71 out of 72 lesions. The global PI-RADS score of the dominant lesion was significantly higher in patients with PCa (4.0 ± 1.3) compared to patients with negative histopathology (2.6 ± 0.8; p = 0.0006). Using a global PI-RADS score cut-off ≥4, a sensitivity of 85 %, a specificity of 82 % and a negative predictive value of 92 % were achieved. CONCLUSIONS: The described fusion system is dependable and efficient for targeted MRI/TRUS fusion-guided biopsy. mpMRI PI-RADS scores combined with a novel real-time MRI/TRUS fusion system facilitate sufficient diagnosis of PCa with high sensitivity and specificity.

En bloc resection of urothelium carcinoma of the bladder (EBRUC): a European multicenter study to compare safety, efficacy, and outcome of laser and electrical en bloc transurethral resection of bladder tumor.

PURPOSE: En bloc resection of bladder tumors (ERBT) may improve staging quality and perioperative morbidity and influence tumor recurrence. This study was designed to evaluate the safety, efficacy, and recurrence rates of electrical versus laser en bloc resection of bladder tumors. METHODS: This European multicenter study included 221 patients at six academic hospitals. Transurethral ERBT was performed with monopolar/bipolar current or holmium/thulium laser energy. Staging quality measured by detrusor muscle involvement, various perioperative parameters, and 12-month follow-up data was analyzed. RESULTS: Electrical and laser ERBT were used to treat 156 and 65 patients, respectively. Median tumor size was 2.1 cm; largest tumor was 5 cm. Detrusor muscle was present in 97.3 %. A switch to conventional TURBT was significantly more frequent in the electrical ERBT group (26.3 vs. 1.5 %, p < 0.001). Median operation duration (25 min), postoperative irrigation (1 day), catheterization time (2 days), and hospitalization (3 days) were similar. Overall complication rate was low (Clavien ≥ 3, n = 6 [2.7 %]). Hemoglobin was significantly lower after electrical ERBT (p = 0.0013); however, overall hemoglobin loss was not clinically relevant (0.38 g/dl). Patients (n = 148) were followed for 12 months; 33 (22.3 %) had recurrences. In total, 63.6 % recurrences occurred outside the ERBT resection field. No difference was noted between ERBT groups. CONCLUSIONS: ERBT is safe and reliable regardless of the energy source and provides high-quality resections of tumors >1 cm. Recurrence rates did not differ between groups, and the majority of recurrences occurred outside the ERBT resection field.

Acceptance, Prevalence and Indications for Robot-Assisted Laparoscopy - Results of a Survey Among Urologists in Germany, Austria and Switzerland.

BACKGROUND: Robotic-assisted laparoscopy (RAL) is being widely accepted in the field of urology as a replacement for conventional laparoscopy (CL). Nevertheless, the process of its integration in clinical routines has been rather spontaneous. OBJECTIVE: To determine the prevalence of robotic systems (RS) in urological clinics in Germany, Austria and Switzerland, the acceptance of RAL among urologists as a replacement for CL and its current use for 25 different urological indications. MATERIALS AND METHODS: To elucidate the practice patterns of RAL, a survey at hospitals in Germany, Austria and Switzerland was conducted. All surgically active urology departments in Germany (303), Austria (37) and Switzerland (84) received a questionnaire with questions related to the one-year period prior to the survey. RESULTS: The response rate was 63%. Among the participants, 43% were universities, 45% were tertiary care centres, and 8% were secondary care hospitals. A total of 60 RS (Germany 35, Austria 8, Switzerland 17) were available, and the majority (68%) were operated under public ownership. The perception of RAL and the anticipated superiority of RAL significantly differed between robotic and non-robotic surgeons. For only two urologic indications were more than 50% of the procedures performed using RAL: pyeloplasty (58%) and transperitoneal radical prostatectomy (75%). On average, 35% of robotic surgeons and only 14% of non-robotic surgeons anticipated RAL superiority in some of the 25 indications. CONCLUSIONS: This survey provides a detailed insight into RAL implementation in Germany, Austria and Switzerland. RAL is currently limited to a few urological indications with a small number of high-volume robotic centres. These results might suggest that a saturation of clinics using RS has been achieved but that the existing robotic capacities are being utilized ineffectively. The possible reasons for this finding are discussed, and certain strategies to solve these problems are offered.